Multi-channel brain or cortical activity monitoring and method

ABSTRACT

The present invention relates to a quantitative electroencephalogram (QEEG) monitor and system capable of monitoring and displaying simultaneously neuropathological characteristic and activity of both sides of a subject&#39;s brain. The methods include various indices and examination of differences in these indices by which neurophysiological conditions or problems can be identified and treated. These methods, and the systems and devices using these methods preferably can be used for identifying these neurophysiological conditions or brain dysfunction with monitors and methods for seizure detection, for sedation monitoring, for anesthesia monitoring, and the like. These bilateral brain monitoring methods and systems, and the devices using these methods can be used by individuals or clinicians with little or no training in signal analysis or processing. These bilateral monitoring methods can also be used in a range of applications.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to processing, monitoring and display ofsignals, and particularly to the processing, monitoring and display ofelectrophysiological signals. More particularly, the present inventionrelates to the processing, monitoring and display ofelectroencephalography (EEG) signals representing cortical/brainactivity. Further, the present invention relates to a method andapparatus for displaying separate electrophysiological signals andquantitative process parameters based on these signals and representingthe cortical or brain activity of each of the subject's brainhemispheres on the same screen, simultaneously. Even further, thepresent invention, while displaying cortical or brain activity signals,relates to methods for measuring signal quality, detectingneuropathological activity in the subject, and detecting changes insubject's status.

2. Technology Review

Quantitative electroencephalograph (QEEG) monitoring is a valuablenon-invasive tool for monitoring brain activity and detecting numerousforms of neuropathological activity such as seizure and stroke. However,traditional QEEG monitoring techniques focus on the subject's brain as awhole, looking at cortical/brain activity. While this type of monitoringis very useful and even necessary to detect certain neuropathologicalactivity or for certain procedures, such as measuring subject statuswith respect to sedation or anesthesia or reaction to noxiousstimulation such as surgical stimulation, detecting seizures during themonitoring procedure, or detecting brain damage, it cannot always detectother problems or conditions that may arise or exist within oneparticular brain hemisphere or as a function of the communicationbetween the two brain, hemispheres.

These problems may include varying levels of sedation betweenhemispheres; seizure or stroke related to one side of the brain; orother neuropathological problems. While bilateral brain monitoringmethods have been proposed and even utilized for basic monitoring of asubject's two brain hemispheres individually and simultaneously, thefocus of such existing methods has been solely based on the patient'sstate of consciousness by means of brain/cortical activity and thisactivity circuitously is based on the whole brain rather than theactivity of each hemisphere. These methods have ignored the potentialfor essentially real-time detection of presently occurringneuropathological activity or of the diagnosis or identification andlocation of such past neuropathological activity particularly where thedifferences between hemispheric activity is indicative of such problems.

It is therefore an object of the present invention to provide a device,system, monitor and method that meets all of these needs and otherswhere such a device and method is applicable. It is another object ofthe present invention that this device and method accurately detect anddisplay information simultaneously regarding a subject's brain activityor cortical state and potential neuropathological activity for bothhemispheres of the subject's brain. It is still another object of thepresent invention that this device and method be usable by technicians,clinicians, caregivers, emergency response technicians, or anyone elsewith appropriate specialized medical training to monitor a subject'sbrain or cortical activity as well as by such persons with littlespecialized training, but in the position to monitor a subject forneuropathological activity that may occur. Finally, it is an object ofthe present invention that this device that a patient's diagnosis andtherapeutic treatment be more accurately determined based on the betterdiagnostic data from the testing and monitoring of the patient.

SUMMARY OF THE INVENTION

The present invention relates to a physiological monitor and system,more particularly to a quantitative electroencephalogram (QEEG) monitorand system, even more particularly to a QEEG monitor and system capableof monitoring and displaying signals from each brain hemisphereseparately and simultaneously or substantially so to determineunderlying neurophysiological problems or also problems related to themeasuring device and system.

Bilateral QEEG signal monitoring is a method for the individual, andessentially simultaneous monitoring, measuring, and displaying of EEGactivity for each hemisphere of a subject's brain, as well as for thecalculation and display of a QEEG index relating to brain or corticalactivity and corresponding to the level of activity in each of thosebrain hemispheres. By examining differences in the indices correspondingto each of those brain hemispheres neurophysiological conditions and/orother problems can be identified and treated. These methods may also beused similarly with the quantification of other physiological signalssuch as electrooculography (EOG), electromyography (EMG),electrocardiography (ECG), electrical impedance tomography (EIT), andthe like.

These methods, and the systems and devices using these methodspreferably can be used for identifying these neurophysiologicalconditions or brain dysfunction with monitors and methods for seizuredetection, for sedation monitoring, for anesthesia monitoring, and thelike. Preferably, these methods, systems and devices can be used inoperating rooms, during acute care such as in intensive care units, orin critical care such as the emergency rooms or in the field. Thesemethods, systems and devices can be used by anesthesiologists, nurseanesthetists, neurologists and neurosurgeons, pulmonologists, emergencyroom physicians and clinicians, intensive care physicians andclinicians, medics, paramedics, emergency medical technicians,respiratory technicians, and the like. Preferably, these methods,systems, and devices using these methods can be used by individuals orclinicians with little or no training in signal analysis or processing.These methods preferably are used with anesthesia monitors, seizuredetectors, sedation monitors, sleep diagnostic monitors, any sort of EEGmonitor, battlefield monitors, operating room monitor, ICU monitor,emergency room monitor, any other sort of ECG monitor, and the like.

The various embodiments of the system of the present invention weredeveloped for monitoring and processing various physiological signalsfrom a subject. Preferably, this system is used for the brain wave oractivity monitoring of a single patient or multiple patients.Preferably, the system is a multi-electrode EEG system; however,depending on purpose of use and cost, systems may have as few as 3electrodes: with at least 2 electrodes for measurement of brain orcortical activity, one for each hemisphere of the subject's rain, and atleast one reference electrode. Preferably, the system or monitor of thepresent invention also includes one or more methods or algorithms fordetecting or quantifying brain or cortical activity, and/or level ofconsciousness, seizure detection, level of sedation and the like.Preferably, the system or monitor can also measure muscle activity, EMGand EOG, contained in the EEG signal, as well as other spectralcomponents of the EEG signal. These components may include but are notlimited to the suppression ratio which is the ratio of time where thereis no substantial brain or cortical activity to the time where there iscortical or brain activity shown in the EEG signal and burst count whichis the number of high frequency bursts. In addition, the system andrelated methods can use other sensors that measure physiological signalswhich directly or indirectly result in or from brain dysfunction, oreffect or result from brain activity.

Preferably, the system or monitor is constructed to be rugged, so as towithstand transport, handling and use in all of the applications listedabove including in emergency scenarios, such as on the battlefield or inmass casualty situations, or to reliably survive daily use by emergencymedical personnel or other first responders. The system or monitorshould preferably be splash-proof (or water tight), dust-tight,scratch-resistant, and resistant to mechanical shock and vibration. Thesystem or monitor should preferably be portable and field-deployable inparticular embodiments to a military theater of operation, the scene ofan accident, the home of a patient, or to any clinical setting.

The system or monitor should preferably be capable of non-expert use. Bythis, it is meant that a person should not be required to possessextraordinary or special medical training in order to use the systemeffectively and reliably. The system should therefore preferably beautomatic in operation in a number of respects. First, the system shouldbe capable of automatic calibration. Second, the system shouldpreferably have automatic detection of input signal quality; forexample, the system should be capable of detecting an imbalance inelectrode impedances, physiological and environmental artifacts, andelectrical interferences and noise. Third, the system should preferablybe capable of artifact detection and removal on one or more levels, soas to isolate for analysis that part of the signal which conveysmeaningful information related to a subject's brain or corticalactivity, level of consciousness, occurrence of a seizure, level ofsedation and the like. Fourth, the system should preferably includeoutputs which result in visual and/or audible feedback capable ofinforming the user of the state of the patient related to quantificationof brain or cortical activity, level of consciousness, occurrence of aseizure, level of sedation and the like at any time during the period oftime that the system was monitoring the patient.

Preferably, the system should operate in real time. One example ofreal-time operation is the ability of the system to detect a seizure orbrain dysfunction event as it is happening, rather than being limited toanalysis that takes place minutes or hours afterward.

The processor or computer, and the methods of the present inventionpreferably contain software or embedded algorithms or steps thatautomatically identity artifacts and even more preferably remove theartifacts from the physiological signal, and automatically quantifybrain or cortical activity, level of consciousness, identify seizures orother brain dysfunction, level of sedation based on the essentiallyartifact free EEG signal.

The system described in this invention also preferably incorporates anumber of unique features that improve safety, performance, durability,and reliability. The system should be cardiac defibrillator proof,meaning that its electrical components are capable of withstanding thesurge of electrical current associated with the application of a cardiacdefibrillator shock to a patient being monitored by the system, and thatthe system remains operable after sustaining such a surge. The systemshould have shielded leads so as to reduce as much as possible theeffects of external electromagnetic interference on the collection ofbiopotential or physiological signals from the patient being monitoredby the system. The system should be auto-calibrating, more preferablycapable of compensating for the potential differences in the gains ofthe input electrodes to the patient module. The system should be capableof performing a continuous impedance check on its electrode leads toensure the suitability of monitored signals.

One embodiment of the present invention is a method of determining EEGsignal quality in a device for quantifying brain or cortical activityduring sedation or anesthesia comprising steps of monitoring a subjectwith a brain having a left hemisphere and a right hemisphere, by hookingthe subject up to a brain or cortical activity quantification devicewith at least two measurement electrodes, and at least one referenceelectrode, the at least two measurement electrodes comprising at leastone EEG electrode, having a signal, positioned to monitor lefthemisphere brain or cortical activity and at least one EEG electrode,having a signal, positioned to monitor right hemisphere brain orcortical activity of the subject's brain, the reference electrodecomprising at least one EEG electrode, each electrode providing an EEGsignal to a processor, measuring the brain or cortical activity of boththe subject's left and right brain hemispheres essentiallysimultaneously, calculating with the processor corresponding indicesrelating to the brain or cortical activity of both the left and righthemisphere of the subject's brain, transmitting the indices from theprocessor to a monitor, displaying both of the indices on a monitorsimultaneously, comparing the indices of each hemisphere's corticalactivity, and determining whether the signal of at least one of the EEGelectrodes is likely to have too high of an impedance. Input signalquality can be affected by an imbalance in electrode impedances,physiological and environmental artifacts, and electrical interferencesand noise, among other factors, and the calculated QEEG indices can beused to display these factors.

Another embodiment of the present invention is a method of detectingneuropathological activity with a device for quantifying brain orcortical activity in a subject during sedation or anesthesia comprisingthe steps of monitoring a subject with a brain having a left hemisphereand a right hemisphere, by hooking the subject up to a brain or corticalactivity quantification device with at least two measurement electrodes,and at least one reference electrode, the at least two measurementelectrodes comprising at least one EEG electrode, having a signal,positioned to monitor left hemisphere brain or cortical activity and atleast one EEG electrode, having a signal, positioned to monitor righthemisphere brain or cortical activity of the subject's brain, thereference electrode comprising at least one. EEG electrode, eachelectrode providing an EEG signal to a processor, measuring the brain orcortical activity of both the subject's left and right brain hemispheresessentially simultaneously, calculating with the processor correspondingindices relating to the brain or cortical activity of both the left andright hemisphere of the subject's brain, transmitting the indices fromthe processor to a monitor, displaying both of the indices on a monitorsimultaneously, comparing the indices of each hemisphere's corticalactivity, and determining whether the brain or cortical activity of onehemisphere of the brain is indicative of a neuropathological conditionwhen compared to the brain or cortical activity of the other hemisphereof the brain of the subject.

Still another embodiment of the present invention is a method ofdetecting a sudden change in subject status with a device forquantifying brain or cortical activity in the subject during sedation oranesthesia comprising the steps of monitoring a subject with a brainhaving a left hemisphere and a right hemisphere, by hooking the subjectup to a brain or cortical activity quantification device with at leasttwo measurement electrodes, and at least one reference electrode, the atleast two measurement electrodes comprising at least one EEG electrode,having a signal, positioned to monitor left hemisphere brain or corticalactivity and at least one EEG electrode, having a signal, positioned tomonitor right hemisphere brain or cortical activity of the subject'sbrain, the reference electrode comprising at least one EEG electrode,each, electrode providing a EEG signal to a processor, measuring thebrain or cortical activity of both the subject's left and right brainhemispheres essentially simultaneously, calculating with the it)processor corresponding indices relating to the brain or corticalactivity of both the left and right hemisphere of the subject's brain,transmitting the indices from the processor to a monitor, displayingboth of the indices on a monitor simultaneously, comparing the indicesof each hemisphere's cortical activity, and determining whether thebrain or cortical activity of one hemisphere of the brain is indicativeof a change in subject status when compared to the brain or corticalactivity of the other hemisphere of the brain of the subject. Thischange in subject status can be a change in level of wakefulness orawareness, or a reaction to noxious or surgical stimulation.

Yet another embodiment of the present invention is a method ofperforming closed-loop anesthesia or sedation to a subject with a devicefor quantifying brain or cortical activity comprising the steps ofmonitoring a subject with a brain having a left hemisphere and a righthemisphere, by hooking the subject up to a brain or cortical activityquantification device with at least two measurement electrodes, and atleast one reference electrode, the at least two measurement electrodescomprising at least one EEG electrode, having a signal, positioned tomonitor left hemisphere brain or cortical activity and at least one EEGelectrode, having a signal, positioned to monitor right hemispherebrain, or cortical activity of the subject's brain, the referenceelectrode comprising at least one EEG electrode, each electrodeproviding a EEG signal to a processor, measuring the brain or corticalactivity of both the subject's left and right brain hemispheresessentially simultaneously, calculating with the processor correspondingindices relating to the brain or cortical activity of both the left andright hemisphere of the subject's brain, transmitting the indices fromthe processor to a monitor, displaying both of the indices on a monitorsimultaneously, comparing the indices of each hemisphere's corticalactivity, and determining the subject's need for additional anestheticor sedation based on a least risk approach calculated by comparing theindices of each hemisphere's cortical activity.

Yet another embodiment of the present invention is a method of providinga message to the user of the device for quantifying brain or corticalactivity during sedation or anesthesia comprising steps of monitoring asubject with a brain having a left hemisphere and a right hemisphere, byhooking the subject up to a brain or cortical activity quantificationdevice with at least two measurement electrodes, and at least onereference electrode, the at least two measurement electrodes comprisingat least one EEG electrode, having a signal, positioned to monitor lefthemisphere brain or cortical activity and at least one EEG electrode,having a signal, positioned to monitor right hemisphere brain orcortical activity of the subject's brain, the reference electrodecomprising at least one EEG electrode, each electrode providing a EEGsignal to a processor, measuring the brain or cortical activity of boththe subject's left and right brain hemispheres essentiallysimultaneously, calculating with the processor corresponding indicesrelating to the brain or cortical activity of both the left and righthemisphere of the subject's brain, comparing with a processor theindices of each hemisphere's cortical activity, and displaying amessage, either audible or visual, or a combination thereof, notifying atechnician, physician, caregiver, or other user that some attention isneeded by the patient and/or brain or cortical activity quantificationdevice.

Additional features and advantages of the invention will be set forth inthe detailed description which follows, and in part will be readilyapparent to those skilled in the art from that description or recognizedby practicing the invention as described herein, including the detaileddescription which follows, the claims, as well as the appended drawings.

It is to be understood that both the foregoing general description andthe following detailed description are merely exemplary of theinvention, and are intended to provide an overview or framework forunderstanding the nature and character of the invention as it isclaimed. It is understood that many other embodiments of the inventionare not directly set forth in this application but are none the lessunderstood to be incorporated by this application. The accompanyingdrawings are included to provide a further understanding of theinvention, and are incorporated in and constitute a part of thisspecification. The drawings illustrate various embodiments of theinvention and together with the description serve to explain theprinciples and operation of the many embodiments of this invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1. Flowchart depicting a processes of detecting signal quality.

FIG. 2. Flowchart depicting a process of detecting past or presentneuropathological activity in the subject's brain.

FIG. 3. Flowchart depicting a process of detecting changes in thesubject's brain or cortical activity.

FIG. 4. Flowchart depicting a closed-loop medication delivery system formaintaining sedation or anesthetization of a subject.

FIG. 5. Flowchart depicting a process of delivering a message to acaregiver based on the calculated brain or cortical activity indicesthat a subject requires attention.

FIG. 6. Image showing a representation of two brain or cortical activityindices calculated for each of a subject's brain hemispheres.

FIG. 7. Image demonstrating brain or cortical activity indices for eachof a subject's brain hemispheres along with corresponding EEG waveformsfrom each hemisphere, other physiological signals being collected (e.g.EMG), as well as the status of the electrode signal quality.

FIG. 8. Image showing QEEG index relating to brain or cortical activityfor each of a subject's brain hemispheres along with the correspondingEEG waveforms from each hemisphere.

FIG. 9. Image of an electrode impedance and signal quality check with aresulting message indicating that the signal from one of the electrodesis bad due to high electrical impedance.

FIG. 10. Image depicting QEEG index relating to brain or corticalactivity for each of a subject's brain hemispheres along with thecorresponding EEG waveforms from each hemisphere, as well as quantifiedmeasurements of electrode signal quality.

FIG. 11. Image demonstrating brain or cortical activity indices for eachof a subject's brain hemispheres along with corresponding EEG waveformsfrom each hemisphere, and spectral powers graphs of each brainhemisphere's cortical activity.

FIG. 12. Image depicting a spider chart of numerous calculated QEEGindices corresponding to various phenomena within the EEG signal.

DETAILED DESCRIPTION OF THE DRAWINGS

The present invention relates to a physiological monitor and system,more particularly to an electroencephalogram (EEG) monitor and system,even more particularly to a QEEG (quantitative electroencephalogram)monitor and system capable of monitoring and displaying signals fromeach brain hemisphere separately and simultaneously.

For the present invention the subject whose EEG signal is being measuredcan be any type of animal, preferably a mammal, most preferably a human.Also, caregiver is understood to include not only those skilled in theuse of EEG equipment and methodologies, such as doctors, physicians,anesthesiologists, EEG technologists, emergency response personnel,nurses, and the like, but also home care individuals, such as familymembers or other non-medically trained persons who may be responsiblefor caring for individuals in need of such equipment at home withminimal additional training.

Various embodiments of the methods of the present invention include oneor more of the following steps, and variations thereof. These stepsinclude monitoring a subject with a brain having a left hemisphere and aright hemisphere, by hooking the subject up to a brain or corticalactivity quantification device with at least two measurement electrodes,and at least one reference electrode, the at least two measurementelectrodes comprising at least one EEG electrode, having a signal,positioned to monitor left hemisphere brain or cortical activity and atleast one EEG electrode, having a signal, positioned to monitor righthemisphere brain or cortical activity of the subject's brain, thereference electrode comprising at least one EEG electrode, eachelectrode providing an EEG signal to a processor.

This step includes using at least one sensor to measure a subject'sbrain wave signals over a period of time. The brain wave or EEG signalscan be obtained by any method know in the art, or subsequently developedby those skilled in the art to detect these types of signals. Sensorsinclude but are not limited to electrodes or magnetic sensors. Sincebrain wave signals are, in general, electrical currents which produceassociated magnetic fields, the present invention further anticipatesmethods of sensing those magnetic fields to acquire brain wave signalssimilar to those which can be obtained through for example an electrodeapplied to the subject's scalp. The subject(s) referred to in thepresent invention can be any form of animal. Preferably the subject(s)are mammal, and most preferably human.

If electrodes are used to pick up the brain wave signals, theseelectrodes may be placed at one or several locations on the subject(s)′scalp. The electrode(s) can be placed at various locations on thesubject(s) scalp in order to detect EEG or brain wave signals. Commonlocations for the electrodes include frontal (F), parietal (P), anterior(A), central (C) and occipital (O).

In order to obtain a good EEG or brain wave signal it is desirable tohave low impedances for the electrodes. Typical EEG electrodesconnections may have impedance in the range of from 5 to 10 K ohms. Itis, in general, desirable to reduce such impedance levels to below 2 Kohms. Therefore a conductive paste or gel may be applied to theelectrode to create a connection with impedance below 2 K ohms.Alternatively, the subject(s) skin may be mechanically abraded, theelectrode may be amplified or a dry electrode may be used. Dryphysiological recording electrodes of the type described in U.S. Pat.No. 6,785,569 can be used. U.S. Pat. No. 6,785,569 is herebyincorporated by reference. Dry electrodes provide the advantage thatthere is no gel to dry out, no skin to abrade or clean, and that theelectrode can be applied in hairy areas such as the scalp.

Additionally if electrodes are used as the sensors, preferably at leastthree electrodes are used—one measurement electrode for an EEG signalfrom the subject's left brain hemisphere, one measurement electrode foran EEG signal from the subject's right brain hemisphere, and onereference electrode; and if further EEG or brain wave signal electrodesare desired the number of electrodes required will depend on whetherseparate reference electrodes or a single reference electrode is used.Each desired electrode of EEG signal requires two measurementelectrodes, one for each brain hemisphere. For the various embodimentsof the present invention, preferably an electrode is used and theplacement of at least one of the electrodes is at or near the occipitallobe of the subject's scalp.

Preferably, the physiological electrodes or other sensors are placed onthe subject's head with at least one measurement electrode on each sideof the subject's head (i.e. left and right sides as divided by thesagittal physiological plane). Also preferably, at least one referenceelectrode needs to be placed in order to obtain and measure thedifferential EEG signals from each of the measurement electrodes. Inorder to be able to compare the signals from the left and righthemispheres of the subject's brain, the reference electrode ispreferably placed as close as possible to the center of the subject'shead. This placement should coincide with the location of thelongitudinal fissure. When placed as close to the longitudinal fissureas possible, the reference electrode will receive EEG signals from bothhemispheres of the subject's brain, and therefore produces a commonsignal that can be used to create accurate and comparable differentialcalculations between the EEG signals measured from each individual brainhemisphere.

Though the measurement electrodes can be placed in any position on thesubject's head where they are able to distinguish between EEG signalsfrom specific 2 s hemispheres of the subject's brain, the electrodes aremost preferably placed in a symmetrical pattern. A symmetrical electrodearray can be used to provide this symmetrical pattern. If a symmetricalelectrode array is used this would allow for placement of electrodes ina manner such that they are in substantially identical placement oneither side (a side being the right or left as separated along thesagittal plane of the body) of the subject's head. This means that theelectrodes in the array are placed substantially equidistant from thecenter of the subject's head, or from the longitudinal fissure which isthe crevice or separation between the left and right hemispheres of thebrain. For example, if a measurement electrode is placed on the leftside of the subject's head, on the left temple, next to the left eye, inorder to measure EOG activity, then likewise a measurement electrodeshould be placed on the right side of the subject's head, on the righttemple, next to the right eye. As with the above non-symmetricalelectrode placement technique, at least one reference electrode ispreferably placed on the subject's head, as near to the longitudinalfissure or center of the subject's head along the sagittal plane, aspossible.

If an electrode array is used, preferably the array is a 3 electrodearray, more preferably a 5 electrode array, and most preferably a 7electrode array. Electrode arrays with 4 and 6 electrodes and with 2reference electrodes per array can be used as well. If 2 or morereference electrodes are used these electrodes are placed substantiallynear or on the sagittal plane of the subject's head.

Once the patient is correctly attached to the EEG monitoring system theneach electrode that has been attached to the subject can transmit an EEGsignal to the processor. Each of the at least two measurement electrodestransmits a measurement EEG signal which is compared against thecorresponding reference electrode signal. These signals are then used tocalculate the QEEG index relating to brain or cortical activity for eachhemisphere of the subject's brain.

Another step of various embodiments of the present invention includesanesthetizing or sedating the subject. Anesthetization or sedation ofthe subject occurs according to strict guidelines and calculations forthe safe and accurate administering of medication. Anesthetization andsedation techniques that can be used in conjunction with the presentinvention primarily include the administration of gas, intravenousmedication delivery, but also any other methods that may be used.

Anesthesia is the general term for methods of blocking a subject'ssensations, primarily of pain (analgesia), and/or movement, as well asmemory (amnesia), for the purposes of performing surgical or othermedical treatment on a subject. Anesthesia can be general, rendering thesubject completely unconscious and blocking sensation over the entirebody, or local, which blocks the sensation of just a small area of thebody. It is general anesthesia to which the methods of the presentinvention are concerned. General anesthesia is generally administeredvia inhalation of anesthetic gas (e.g. Isoflurane, Desflurane, etc.) orintravenous anesthetic (e.g. Propofol, Lorazepam, Midazolam, Thiopental,Diazepam, etc), but other forms of medications that can be given as partof the anesthesia scheme or in conjunction therewith includingsedatives, beta-blockers, neuromuscular blockage agents,vaso-constrictors, vaso-dilators and the like are considered as well.Inhaled anesthetics are generally applied by placing an anesthesia maskover the subject's mouth and nose and supplying the anesthetic gasthrough the mask so the subject inhales it while breathing in until ittakes effect and renders the subject unconscious. Intravenousanesthetics are administered by placing an intravenous catheter into thesubject, and either injecting the anesthetic via syringe into theinjection port of the catheter or attaching a hose from the anestheticsupply to the connecting hub of the catheter and allowing the anestheticto drip and infuse into the subject's blood stream. Other methods foradministering anesthetic medication are also available and can beutilized with the present invention, and future methods developed bythose skilled in the art will be applicable to the present invention aswell.

Anesthesia serves clear and welt-known benefits in the clinical andhospital setting. Patients undergoing surgery are quite often subjectedto anesthesia to block the pain arising from the surgical procedures aswell as to render them motionless for the purposes of performing thesurgical procedures.

Sedation is a process by which a subject is calmed or anxiety isreduced. Sedatives are often used in conjunction with anesthetics todull pain from medical procedures as sedation does not have an analgesiceffect on its own. Similar to the various forms of anesthesia, sedationis commonly obtained through the administering of a sedative viainhalation or intravenous catheter. Common sedatives used in medicalprocedures include clonazepam, phenobarbitol, and the like.

Sedation is very useful in areas such as the hospital ICU where,relating to the present invention, it is often necessary to keep thepatient subdued to monitor brain function as he or she recovers frombrain surgery or other injury, or to prevent him or her from fightingthe equipment to which he or she is attached, such as a ventilator. Inmany situations, particularly in the event of brain surgery or injury,EEG monitoring is necessary to ensure that a patient's is recovering andfunctioning normally. Sedation prevents the patient from becomingagitated and interfering with the EEG monitoring process by movingexcessively or by removing the monitoring sensors. Additionally,patients often are required to use ventilators to assist in breathingand many find ventilator tubes to be very uncomfortable and evenpainful, and are very prone to pulling or yanking the tubes out, despitethe fact that they will likely have trouble breathing without it.Sedating the patient helps to alleviate their discomfort (if combinedwith an analgesic agent) or simply tranquilizes them so they cannot pullat the tubes and cause themselves further harm. Further, patients onventilators often instinctively “fight” the ventilator, which is theyattempt to breath in a different pattern than that set by the ventilatorcausing anxiety or panic with the patient. Many times a patient is oversedated in order to prevent this anxiety or panic. Over sedating thepatient results in higher infection rates as well as longer periods oftime necessary to wean the patient from the ventilator.

Another situation where anesthesia and/or sedation are required isduring artificially induced coma. Severe brain trauma and neurosurgeryare circumstances where it may be necessary to induce a coma with theuse of anesthesia. Artificial comas are generally induced withbarbiturates, such as pentobarbital or thiopental, because such drugsreduce the metabolic rate of brain tissue as well as cerebral blood flowwhich narrows the blood vessels in the brain and reduces pressure andswelling. The theory supporting such treatment is that it helps toprevent further brain damage in cases of injury and to preventrestriction on the neurosurgeon's ability to perform the necessarytasks. During such treatments or situations, brain or cortical activitymonitoring is necessary to ensure the health and safety of the patient.

Another step of various embodiments of the present invention includesmeasuring the brain or cortical activity of both the subject's left andright brain hemispheres essentially simultaneously. In order to measurethe brain or cortical activity from the raw EEG signal, that signal mustbe “pre-processed” in order to get it into a form that is measurable andwhich can provide the pertinent information. Generally, pre-processingsteps include signal amplification, initial hardware filtering methods,artifact detection and removal, analog-to-digital conversion, furthersoftware filtering, and the like. Physiological signals generally needto be amplified because the raw signals are typically at very lowstrength levels that can be difficult to discern. Amplificationmagnifies the signals so that they are more manageable to the particularequipment. Initial hardware filtering methods are used to try tominimize or eliminate any ambient signal interference (e.g.electromagnetic interference) that can corrupt the desired signal andprevent accurate signal analysis. Additional filtering such as artifactdetection processes identify further signal perturbations including, butnot limited to other signals such as electromagnetic interference thatwas not filtered out, and in the case of EEG monitoring, otherphysiological signals such as EMG, EGG, ECG, and the like. In addition,head or body movements can result in EMG artifacts that need to beremoved as well. Accordingly, QEEG indices can be calculated for each ofthese separate components of the EEG signal and displayed individuallyor in combination with other QEEG indices. Along with detecting theseartifacts it is necessary to try and remove them to leave only theunperturbed, raw signal that is desired, the EEG signal. Digital signalconversion is also required in order to take the raw physiologicalsignal and transform it into an electrical signal that can be measured,analyzed and recorded by the given hardware. Digital signal conversioncan take place also before some or all of the filtering. Once the signalhas undergone both filtering and conversion from analog to digital it isthen ready to undergo the appropriate and necessary analytical andanalysis techniques.

Analytical and analysis techniques are needed to measure criticalfeatures of the EEG signal that allow quantification or QEEG indexing ofthe subject's brain or cortical activity, depth of anesthesia orsedation, wakefulness and awareness, anesthetic state and the like.These analytical and analysis techniques can include the use of spectraland higher order spectral analysis, wavelets, auditory or somatosensoryevoked potentials, and the like. Analytical techniques can include butare not limited to the use of transforms for analyzing and measuringvarious features of the signal. Different transforms that may be usedare Hilbert transform, short-time Fourier transforms, Wignerdistributions, Radon transform, Fast Fourier transform, wavelettransform and the like. The most common technique is the use of spectraland higher order spectral analysis such as Fast Fourier transform. Thepreferred technique is the use of wavelet transform.

As noted above, the measurement of each brain hemisphere's corticalactivity is preferably performed essentially simultaneously.‘Essentially simultaneously’ refers to the preference that theprocessor, or processors, record and measure the EEG signal from theleft brain hemisphere at substantially the same time as the EEG signalfrom the right brain hemisphere is recorded and measured. Preferably,the signals from each hemisphere should be recorded and measured within10 minutes of each other, more preferably within 5 minutes of eachother, even more preferably within 1 minute of each other, still morepreferably within 30 seconds of each other, even still more preferablywithin 10 seconds of each other, even still more preferably within 1second of each other, even still more preferably within 500 millisecondsof each other, more preferably still within 100 millisecond of eachother, even still more preferably within 10 milliseconds of each other,and most preferably within 1 millisecond of each other.

Yet another step of various embodiments of the present inventioninvolves calculating, with a processor, the QEEG indices relating to thebrain or cortical activity corresponding to both the left and righthemisphere of the subject's brain. When the processor is receiving highquality EEG signals from each of the measurement electrodes on each sideof the subject's head as well as the reference electrode, it begins tocalculate the QEEG index relating to brain or cortical activity for eachbrain hemisphere. These QEEG indices are calculated by using thevariations of the transforms listed above or like techniques known inthe art. As mentioned above, the most general technique is through theuse of FFT while the preferred technique is with a wavelet transform.

Spectral and higher order spectral analysis is one technique used toprovide an accurate and reliable QEEG index of brain or corticalactivity. This technique uses a Fast Fourier transform that quantifiesnon-linearities and phase relationships intrinsic to any waveform suchas an EEG signal. Fast Fourier transform analysis is used to take a rawwaveform recorded in the time domain (the particular physiologicalsignal recorded over time) and transform it into the frequencycomponents of that signal or power spectrum at a number of timeintervals.

Although Fast Fourier transformed (FFT) signals are useful fordetermining whether some change, pathological activity, or disturbanceoccurred during the recording of the physiological signal, timeinformation is not present in the Fast Fourier transformed signal. FFTgives what frequency components exist in the signal.

In one embodiment, also described in U.S. Pat. Nos. 4,907,597;5,010,891; 5,320,107 and 5,458,117, which are herein incorporated byreference, a variation of FFT is used as follows. A filtered, digitizedEEG signal recorded over a given period of time is broken down intosmaller sub-segments of time. For example, a two minute long signal canbe divided into four second long intervals creating a set of 30 timeintervals. An FFT analysis is then performed on each interval, and theresulting Fats are then used to produce bispectral complex tripleproduct and bispectral real triple product arrays for that interval. Thecomplex triple product arrays of all intervals are added together, andthe real triple product arrays of all intervals are also added together.Each element in the final complex array and final real array is thendivided by the number of intervals (30 intervals in the above example)to produce an average complex triple product array and an average realtriple product array. The magnitude squared of each element in thecomplex triple product array is divided by the corresponding element inthe real triple product array to form the bicoherence array. Thebicoherence array is displayed on a video terminal or plotted, and isused as a figure of merit for the assessment of cerebral electricalfunction.

Since the bispectral process involves an evaluation of the relationalcomponents of the fundamental constituents of any signal without regardto the absolute magnitudes of the signals, the bispectral decompositionof the EEG signal yields a unique quantitative description of cerebralelectrical behavior. Deviation from normal electrical activity patternsin the brain (whether due to ischemia or anesthesia) will lead to analteration in the “fine fingerprint” embedded in the structure of thesurface EEG signal. Since bispectral analysis is able to extract aquantitative fingerprint inherent in any signal, it provides a uniquequantitative index of the influence of ischemia or anesthetic drugs onelectrical properties and function of the brain.

Wavelet analysis, on the other hand, is a method that extracts time andfrequency information simultaneously addresses some of the limitationsof FFT. For this reason, wavelets are more suitable for the analysis ofnon-stationary or transitory features, which characterize most signalsfound in biomedical applications. Wavelet analysis uses waveletstransforms for signal decomposition. Wavelet analysis can be viewed as ageneralization of Fourier analysis since it introduces time localizationin addition to frequency decomposition of a signal. Instead of Fourieranalysis which discards time information, wavelets are capable ofcapturing signal features such as small-scale transients, breakpoints,discontinuities as well as general trends and self-similarity. Thesefeatures cannot be measured by classical spectral techniques. Inaddition, wavelets—classes of wave-like functions with a finite numberof oscillations, an effective length of finite duration and no offsetcomponent-form a basis for the lossless decomposition of a given signal.

The use of wavelet transform significantly reduces the computationalcomplexity when performing the task of assessing the subject's brainactivity or cortical state based on an acquired EEG signal. Neither alarge number of reference signals nor an extensive amount of clinicalEEG data is needed to produce the QEEG index of brain or corticalactivity. The methodology of wavelet analysis may also be used toascertain the state of the brain and the well being of the CNS beyondascertaining the effects of anesthetic agents on the brain. It may alsobe used to discriminate between different sleep stages, to assessalertness/drowsiness levels in subjects performing safety criticalactivities, to evaluate cognitive states such as postoperative andICU-related cognitive impairment or Alzheimer-related impairment, todetect pre-ictal patterns in order to predict epileptic seizures, topredict seizure duration such as in Electro Convulsive Therapy, torecognize various pathological states of the CNS such as sleepdisorders, depression, addiction, ADHD or other psychiatric disorders,to monitor the changes in the cerebral metabolic rate, to establish theblood characteristic at the cortical level, to obtain pharmacodynamicmodels of anesthetic and other neurological and psychoactive drugs, orto develop titration and dosing profiles for such drags.

Wavelet analysis represents a signal as a weighted sum of shifted andscaled versions of the original waveform, without any loss ofinformation. A single wavelet coefficient is obtained by computing thecorrelation between the scaled and time shifted version of the origin alwaveform and the analyzed part of a signal. For efficient analysis,scales and shifts take discrete values based on powers of two (i.e., thedyadic decomposition). Wavelet analysis utilizes a hierarchical signaldecomposition, in which a given signal is decomposed by a series of low-and high-pass filters followed by down-sampling at each stage. Thisanalysis is referred to as Discrete Wavelet Transform (DWT). Theparticular structure of the filters is determined by the particularwavelet family used for data analysis and by the conditions imposed fora perfect reconstruction of the original signal.

The approximation is the output of the low-pass filter, while the detailis the output of the high-pass filter. In a dyadic multiresolutionanalysis, the decomposition process is iterated such that theapproximations are successively decomposed. The original signal can bereconstructed from its details and approximation at each stage (e.g.,for a 3-level signal decomposition, a signal S can be written asS=A3+D3+D2−D1). The decomposition may proceed until the individualdetails consist of a single sample. The nature of the process generatesa set of vectors (fort instance a.sub.3, d.sub.3, d.sub.2, and d.sub.1in the three level signal decomposition), containing the correspondingcoefficients. These vectors are of different lengths, based on powers oftwo. These coefficients are the projections of the signal onto theoriginal waveform at a given scale. They contain signal information atdifferent frequency bands determined by the filter bank frequencyresponse. DWT leads to an octave band signal decomposition that dividesthe frequency space into the bands of unequal widths based on powers oftwo.

The Stationary Wavelet Transform (SWT) is obtained in a similar fashion;however, the down-sampling step is not performed. This leads toredundant signal decomposition with better potential for statisticalanalysis. The frequency space division is the same as for DWT.

Despite its high efficiency for signal analysis, DWT and SWTdecompositions do not provide sufficient flexibility for a narrowfrequency bandwidth data analysis. Wavelet packets, as a generalizationof standard DWT, alleviate this problem. At each stage, details as wellas approximations are further decomposed into low and high frequencysignal components. Accordingly, a given signal can be written in a moreflexible way than provided by the DWT or SWT decomposition (e.g., atlevel 3 we have S=A1+AD2+ADD3+DDD3, where DDD3 is the signal componentof the narrow high frequency band ddd.sub.3). Wavelet packet analysisresults in signal decomposition with equal frequency bandwidths at eachlevel of decomposition. This also leads to an equal number of theapproximation and details coefficients, a desirable feature for dataanalysis and information extraction.

In one embodiment, also described in U.S. Pat. No. 7,373,198, which ishereby incorporated by reference, a variation of this wavelet transformmethod is used for EEG analysis as follows. An observed data set isacquired in real-time from a subject's EEG signal. This data set iscompared, substantially in real time, with one or more reference datasets which characterize distinct anesthetic states. The comparisonyields a QEEG index of brain or cortical activity. This QEEG index canthen be used to assist in distinguishing the various stages of generalanesthesia, in distinguishing increasing and decreasing depths ofgeneral anesthesia, and in detecting the loss of consciousness duringthe induction of general anesthesia, thus providing an endpoint forindividual titration of intravenous induction agents.

The observed and reference data sets are statistical representations ofthe wavelet coefficients obtained by applying a wavelet transform ontocorresponding observed and reference signals. These coefficients may beobtained through a wavelet transform of the EEG such as standard dyadicdiscrete wavelet transform (DWT), discrete stationary wavelet transform(SWT), or wavelet packet transform. In this respect, filters yieldingcoefficients in a frequency band, chosen such that their statisticalrepresentation differentiates between anesthetic states, can be used forthis type of analysis. The observed and reference data sets are obtainedby calculating a statistical representation of the transformationcoefficients. The methodology of this invention may also be used forextracting information from other physiological signals, such asElectrocardiogram (ECG), representing measured cardiac activity of asubject in order to evaluate the state of the autonomous nervous systemof the subject.

The reference data sets represent distinct anesthetic states taken fromthe continuum from conscious (i.e., fully awake) to isoelectric EEG(i.e., no more brain activity). They are extracted off-line from a groupof subjects or patients. They are then stored for substantiallyreal-time implementation. The transformation selected maximizes thedissimilarity between each of the reference data sets.

The comparison between the observed data set against the reference datasets can be based on the computation of the correlation between thesefunctions. However, a computationally less demanding solution is toquantify the similarity between these functions by computing the L1(Manhattan), L2 (Euclidean), or any distance metrics. In the preferredembodiment, where two reference data sets are used, the result of thiscomparison yields two values, each expressing the likelihood of apatient being awake or anesthetized. These two values are furthercombined into a single value corresponding to a univariate QEEG index ofbrain or cortical activity.

Another step of various embodiments of the present invention involvestransmitting the brain or cortical activity indices from the processorto a monitor. The processor calculates the brain or cortical activityindices substantially in real time as it receives the EEG signal fromeach electrode attached to the subject, and transmits those indices to amonitor for display. This occurs as an electrical signal from theprocessor containing the current QEEG index relating to brain orcortical activity for a given brain hemisphere which is sent along videoconnection wires which are attached to the monitor that displays theresultant visual depiction of the indices.

Alternatively, the signal could be broadcast wirelessly from theprocessor via WiFi network, or a medical band or Bluetooth RF connectionto a monitor equipped to receive such signals. The brain or corticalactivity indices can be transmitted from the processor to a monitor viathese or any other currently available communication methods for visualdisplays or any that may become available in the future.

Preferably, when using a radio frequency method the system will transmitdata in a frequency range, or band, such that it will not receiveinterference from other radio frequency signals. Preferably, the systemwill transmit below a frequency of 2.0 GHz to avoid frequency bands thatare highly congested, namely the 2.4 GHz band. Operation within thesebands over 2.0 GHz may make interference problematic such as by limitingusable bandwidth. Additionally, if power is constant then operation atlower frequencies allows for greater operational range than at higherfrequencies. Conversely, operation at lower frequencies consumes lesspower than higher frequencies over the same range.

Another step of various embodiments of the present invention involvesdisplaying both of the indices on a monitor simultaneously. As theprocessor is essentially continuously calculating the brain or corticalactivity indices for each of the subject's brain hemispheres, it alsoessentially continuously transmits both indices as described above to amonitor. The monitor(s) receives said signal from the processor anddisplays the indices corresponding to each of the subject's brainhemispheres adjacent to each other. The QEEG index displays can beoriented vertically (one QEEG index above the other) or horizontally(the two indices side by side). Preferably, each QEEG index is labeledwith the corresponding hemisphere (i.e. left or right) which itrepresents. This label can be provided in text, by the orientation ofthe QEEG index displays, or by color coding. Even more preferably, theQEEG index display is color coded to match the color of the electrodeleads attached to the corresponding side of the subject's head. Forexample, if the QEEG index display for the left hemisphere is yellow,and the QEEG index display for the right hemisphere is orange, then theelectrode leads attached to the left side of the subject's head would beyellow and those attached to the right side would be orange.

Additional display options include but are not limited to displaying thetwo indices along with: the raw EEG signals as they are acquired, aspectral density graph of the EEC waveform, a display of the signalquality of the electrodes or other sensors, a message or instructionsfor the caregiver to give the subject attention or perform a task formonitoring, a trend screen showing the history of the brain or corticalactivity indices, waveforms for other signals obtained (i.e. EMC, EOG,and the like), any combination of these or other available displaysand/or the like.

Yet another step of various embodiments of the present inventionincludes comparing the indices of each hemisphere's brain or corticalactivity. As the processor measures the EEG activity of each of thesubject's brain hemispheres and calculates the corresponding brain orcortical activity indices, it also performs a comparison of those twoindices substantially in real time. The system notifies the caregiverthat there is a potential problem (i.e. signal quality has decreased,subject is showing signs of arousal in one brain hemisphere, subject isexperiencing some neuropathological activity, and the like) preferablywhen the difference between the indices for the left and righthemispheres is greater than 5%, more preferably when the difference isgreater than 10%, even more preferably when the difference is greaterthan 12%, still more preferably when the difference is greater than 15%and most preferably when the difference is greater than 20%. Smalldifferences in the indices less than 5% are usually common in normalfunctioning brain activity, and notification of differences in thatrange would present an increase in false diagnosis of problems.

Another step of various embodiments of the present invention includesdetermining whether the signal of at least one of the EEG electrodes islikely to have too high of impedance. One object of the presentinvention is to use the calculated brain or cortical activity indicesfrom each of the subject's brain hemispheres, more particularly thedifference between those indices, to determine whether a problem orcondition exists in measurement or with the subject or patient. If thecalculated indices are too dissimilar, then the system determines theremay be a problem, which may be either poor signal quality or may be aphysiological condition or problem with the subject or patient. To testfor poor signal quality, an electrical impulse is provided to the sensoror electrode and the system measures the resulting electrical impedanceof that sensor or electrode. This can be done automatedly when thedifference between indices is too high, or the system may provide amessage to a caregiver to manually instruct the system to perform thetest. If the measured electrical impedance is high, the caregiver canimprove signal quality by replacing the sensor or electrode, applyingconductive gel and resealing the sensor or electrode, re-abrading thesubject's skin and reapplying the sensor or electrode, or any otheravailable means to address the issue. Electrical impedance can be ashigh as 5 to 10 K ohms in typical electrode connections, but for goodsignal quality, impedance is preferably maintained less than 5 K ohms,more preferably less than 4 K ohms, even more preferably less than threeK ohms, and most preferably at 2 K ohms or less.

Another step of various embodiments of the present invention includesdetermining whether the brain or cortical activity of one hemisphere ofthe brain is indicative of a neuropathological condition when comparedto the brain or cortical activity of the other hemisphere of the brainof the subject. One object of the present invention is to use thecalculated brain or cortical activity indices from each of the subject'sbrain hemispheres, more particularly the difference between thoseindices, to determine whether the subject is experiencing some form ofneuropathological activity (i.e. stroke, seizure, and the like). If thecalculated indices are too dissimilar, then the system determines theremay be a problem, which may be such neuropathological activity (e.g.,include but are not limited to stroke, regional perfusion disturbances,ischemia, metabolic dysfunction, regional seizure, hypotension andhypertension related disturbances, and the like). Once determining thata potential neuropathological activity or disturbance is occurring orhas occurred, the system notifies a physician, clinician, or othercaregiver that such a problem is or has occurred so that person canadminister the proper treatment to the subject or patient.

Similar to above, asymmetry thresholds in the brain or cortical activityindices for each brain hemisphere may be indicative of potentialneuropathological activity, and this will indicate as such when thedifference between the indices for the left and right hemispheres isgreater than 5%, more preferably when the difference is greater than10%, even more preferably when the difference is greater than 12%, stillmore preferably when the difference is greater than 15% and mostpreferably when the difference is greater than 20%. Small differences inthe indices less than 5% are usually common in normal functioning brainactivity, and notification of differences in that range would present anincrease in false diagnosis of problems.

The calculated indices are not used to diagnose the specific type ofneuropathological activity which is or has occurred. EEG signals, andspecifically QEEG, generally only indicate that a problem exists, orrather than some abnormal activity has occurred. The caregiver who readsand interprets these signals has the responsibility to coordinate all ofthe factors surrounding the subject or patient and make a determinationof what the most likely cause of the neuropathological activity is.

Another step of various embodiments of the present invention involvesdetermining whether the brain or cortical activity of one hemisphere ofthe brain is indicative of a change in subject status when compared tothe brain or cortical activity of the other hemisphere of the brain ofthe subject. One object of the present invention is to use thecalculated brain or cortical activity indices from each of the subject'sbrain hemispheres, more particularly the difference between thoseindices, to determine whether the subject is showing signs of muscleactivity as a reaction to some pain or other stimulus, in one hemispherethat is not shown in the other. If the calculated indices are toodissimilar, then the system determines there may be a problem, which mayindicate that the subject's brain is reacting to some condition, event,or occurrence. If one hemisphere of the subject's brain experiences andreacts to pain or noxious stimuli or discomfort and produces involuntaryreactions, the caregiver(s) may assume that additional sedative oranesthetic medication is necessary. However, if the other hemisphere isstill fully anesthetized or sedated when the additional medication isadministered, that hemisphere can be monitored for overdosing. Anotherpossibility when the indices are too dissimilar is that someneuropathological activity may be occurring in one hemisphere, such asstroke, seizure, and the like.

When a subject requires additional sedative or anesthetic medication,the above dosing issues need to be addressed prior to administering saidmedication. One option is to determine whether medication is needed, andthe dose required, based on the brain hemisphere that has the highercalculated QEEG index corresponding to a higher level of alertness,wakefulness or awareness. This method prevents one of the subject'sbrain hemispheres from becoming alert or wakeful enough to becomecognitive of pain or other surrounding circumstances. However, thisleads to the potential of overdosing the brain hemisphere of thesubject's brain that is still adequately sedated or anesthetized.Another option, is to determine whether medication is needed, as well asthe dose required, based on the brain hemisphere that has a lowercalculated QEEG index corresponding to deeper sedation or anesthesia.This method decreases the risk of overdosing either hemisphere of thesubject's brain; however, it increases the risk that one of thesubject's brain hemispheres will become more alert and possibly rise tothe level of cognition of pain or other surrounding circumstances. Thismethod also potentially allows for lower overall dosing of anesthesiadrugs and sedatives.

Other possible options are hybrid, least risk dosing techniques. Oneleast risk approach is to verify that the two indices are similar, andif they are not, the closed-loop system should warn the user and stopadjusting the drug automatically allowing the notified user to monitorthe subject and perform the adjustments as necessary. In this case, thebilateral feature is used for redundancy. Another least risk approach isto have the anesthesiologist choose the index used to titrate the drugif the two indices are significantly different. Another approach is toautomatically make this determination based on agreed-upon rules (forexample, use the index for which the signal quality is better, or alwaysuse the minimum of the two indices, or always use the maximum of the twoindices, or use the average of the two, or use some other linear ornonlinear combination of the two indices depending on the anesthesiadelivery goals and needs). Yet another option would be to select a lowerlimit and an upper limit such that both indices are kept between thesetwo limits. Yet another option would be to select a lower limit suchthat at least one of the indices is kept above this limit. Yet anotheroption would be to select an upper limit such that at least one of theindices is kept below this limit. Other combinations of the tower andupper limits and indices behaviors in relation hip to these limits cambe envisioned based on anesthesia delivery goals and needs, and areintended to be included within the scope of the present invention. Inutilizing this method, preferably the upper limit corresponds to 50%probability of a subject being awake, more preferably to 60% probabilityof a subject being awake, even more preferably to 70% probability of asubject being awake, more preferably still to 80% probability of asubject being awake, yet more preferably to 90% probability of a subjectbeing awake, and even more preferably to 95% probability of a subjectbeing awake. Further, in utilizing this method, preferably the lowerlimit corresponds to 5% suppression of a subject's brain or corticalactivity, more preferably to 10% suppression of a subject's brain orcortical activity, even more preferably to 20% suppression of asubject's brain or cortical activity, stilt more preferably to 30%suppression of a subject's brain or cortical activity, and even morepreferably to 35% suppression of a subject's brain or cortical activity.Further, in utilizing this method, the lower and upper limits can bechosen to correspond to different probabilities of various clinicalendpoints, such as probability of patient movement, probability ofpatient forming memory recall, probability of patient reaction orresponse, probability of patient being hypo- or hyper-tensive, and thelike. Many different combinations of the lower and upper limits andclinical endpoints can be envisioned based on anesthesia delivery goalsand needs, and are intended to be included within the scope of thepresent invention.

Another step of various embodiments of the present invention includesdisplaying a message, either audible or visual, or a combinationthereof, notifying a caregiver that some attention is needed by thepatient and/or brain or cortical activity quantification device. It isnot always immediately apparent simply by looking at the monitor or theindices displayed for the brain or cortical activity of each of asubject's brain hemispheres when there is a potential problem with theequipment or the subject. Furthermore, there are certain circumstances(e.g., long term EEG monitoring and care, sleep studies, and the like)where no caregiver may be actively attending to the subject and monitoron a full-time basis and may not see when the indices indicate apotential problem. For these reasons, the present invention preferablyincludes the ability to display a message or notify a caregiver in someway to tend to the subject. Several types of messages or signals arediscussed below, and can be used individually or in any type ofcombination with each other. This list is by no means exhaustive.

One option for notifying the caregiver is to display a message on themonitor where the brain or cortical activity indices are displayed. Thismessage may be a textual one that scrolls across the screen, flashes onthe screen, appears and blinks, and the like. Furthermore, the caregivermay be alerted by color (e.g., red) to distinguish the message from therest of the monitoring information on the screen. The text itself mayappear in color or may appear in a colored frame or box.

Another option for notifying a caregiver is to display a message on themonitor in the form of a symbol, rather than actual text. Basic shapescan be used to indicate different potential issues that may arise. Thesesymbols may scroll across the screen, flash on the screen, appear on thescreen and blink, and the like. The symbols may also be displayed incolor to distinguish the symbol from the rest of the monitoringinformation on the screen. A symbol can also be used in combination withtext as well.

Yet another option for notifying a caregiver is to sound an audiblesignal or message to get the attention of a caregiver. The audiblesignal can be a tonal sounding, such as a single beep, multiple beeps,or a longer tone. The message could be synthesized speech or aprerecorded message. Furthermore, different combinations of beeps can beused to indicate different possible issues. Any combination of audibleand visual signals and/or messages may also be used. Still anotheroption for notifying a caregiver is to send a message to a pager,computer, PDA (personal digital assistant), cell phone, or phone in casesaid caregiver is not in the immediate vicinity of the subject.

Now referring to the FIGS. 1-11, FIG. 1 is a flow chart describing aprocess for monitoring and measuring electrode signal quality using thebilateral monitoring techniques described herein. A subject is attachedto the bilateral monitoring system with an electrode array that measuressignals from both hemispheres of the subject's brain (not shown).Preferably, the electrode array involves the placement of electrodes onthe subject's head in such a manner that the measurement electrodes aresubstantially equidistant from the center of the subject's head whichcorresponds to the longitudinal fissure of the brain separating the twobrain hemispheres along the sagittal plane of the subject's body. Alsopreferably, at least two measurement electrodes are placed substantiallysymmetrically as described, at least one measurement electrode beingplaced on each side of the subject's head to measure the brain orcortical activity of each brain hemisphere. A reference electrode isplaced in the center of the subject's head, substantially near thelocation of the longitudinal fissure (not shown). Once the electrodearray is in place, the subject's brain or cortical activity in eachbrain hemisphere is monitored at substantially the same time 1.

After monitoring the subject's brain or cortical activity for eachhemisphere, the subject is anesthetized or sedated 3, and when thesubject is fully anesthetized or sedated, the brain or cortical activityin each of the subject's brain hemispheres is then measured individuallybut at substantially the same time 5 and preferably on a continuousbasis. The measurements are performed on each hemisphere via themeasurement electrode on for the given hemisphere and the commonreference electrode along the longitudinal fissure (not shown). As theEEG signal is monitored and measured from each brain hemisphere, thesystem calculates individual brain or cortical activity indices 7 foreach of the subject's brain hemispheres that quantifies the subject'sbrain or cortical activity, corresponds to the level of wakefulness orawareness, or conversely the level of sedation, that each of thesubject's brain hemispheres are experiencing. These brain or corticalactivity indices range between the values of zero (indicating brain,death) and 100 (indicating complete wakefulness and awareness)—howeverother types of indices may be used as well. As these indices arecalculated for each brain hemisphere, they are displayed substantiallyin real time and substantially at the same time on a monitor 9 for thecaregiver to see and use to evaluate the needs of the subject.Optionally, the method can include a warning or message (not shown) tothe caregiver indicating a significant difference between the twoindices. This warning or message can be a flashing light, a message onthe monitor, a bell, or the like.

If the signal quality decreases or becomes compromised, the caregiver,if properly trained should notice the differences in the indices on thescreen and check the electrodes to determine if a problem exists 11.While significant differences in the indices could be indicative ofsignal quality—this could also reflect other physiological conditions ofthe subject as well. There are several common issues that cause adecrease in signal quality, including, but not limited to conductive gelbetween the electrode and subject's skin becoming dry 13, the electrodeitself being bad or failing 17, or the electrode having moved from itsoriginal position 21. If the caregiver finds that differences in theindices are indicative of high impedances in one or more of theelectrodes then the caregiver should check the electrode(s) to see whatpossible issue or problem has caused the poor signal quality and makesthe necessary adjustments to repair the connection and restore goodsignal quality. If the caregiver notices that the conductive gel hasdried up 13 (only an issue with electrodes that require such gel, notwith dry electrodes), then the caregiver simply reapplies conductive gelto the surface of the electrode or the subject's skin and reapplies theelectrode to the subject 15. If it is determined that the electrodeitself is bad 17 and unable to accurately conduct a signal at all, thenthe caregiver discards the bad electrode and replaces it with a new one19 in the same manner and position as the first one was applied. If theelectrode has moved from the position in which it was initially placed21, the caregiver can then reseat the electrode or may need to re-abradethe subject's skin 23 under the electrode before reseating the electrodeinto position in order to retrieve a sufficient signal. Once the problemhas been appropriately addressed, and all of the electrodes areaccurately and sufficiently conducting an EEG signal from the subject tothe system and monitor, the caregiver can then reinitializes 25 orstarts the signal acquisition and subsequent monitoring and measurementof brain or cortical activity in each of the subject's brainhemispheres.

FIG. 2 is a flowchart depicting the process of detecting the presence ofpast or present neuropathological activity in one of the subject's brainhemispheres using the bilateral monitoring system. A subject is attachedto the bilateral monitoring system with an electrode array that measuressignals from both hemispheres of the subject's brain (not shown).Preferably, the electrode array involves the placement of electrodes onthe subject's head in such a manner that the measurement electrodes aresubstantially equidistant from the center of the subject's head whichcorresponds to the longitudinal fissure of the brain separating the twobrain hemispheres along the sagittal plane of the subject's body. Alsopreferably, at least two measurement electrodes are placed substantiallysymmetrically as described, at least one measurement electrode beingplaced on each side of the subject's head to measure the brain orcortical activity of each brain hemisphere. A reference electrode isplaced in the center of the subject's head, substantially near thelocation of the longitudinal fissure (not shown). Once the electrodearray is in place, the subject's brain or cortical activity in eachbrain hemisphere is monitored at substantially the same time 31.

After monitoring the subject's brain or cortical activity for eachhemisphere, the subject is anesthetized or sedated 33, and when thesubject is fully anesthetized or sedated, the brain or cortical activityin each of the subject's brain hemispheres is then measured individuallybut at substantially the same time 35 and preferably on a continuousbasis. The measurements are performed on each hemisphere via themeasurement electrode on for the given hemisphere and the commonreference electrode along the longitudinal fissure (not shown). As theEEG signal is monitored and measured from each brain hemisphere, thesystem calculates individual brain or cortical activity indices 37 foreach of the subject's brain hemispheres that quantifies the subject'sbrain or cortical activity, corresponds to the level of wakefulness orawareness, or conversely the level of sedation, that each of thesubject's brain hemispheres are experiencing. These brain or corticalactivity indices range between the values of zero (indicating braindeath) and 100 (indicating complete wakefulness and awareness)—howeverother types of indices may be used as well. As these indices arecalculated for each brain hemisphere, they are displayed substantiallyin real time and substantially at the same time on a monitor 38 for thecaregiver to see and use to evaluate the needs of the subject.Optionally, the method can include a warning or message (not shown) tothe caregiver indicating a significant difference between the twoindices. This warning or message can be a flashing light, a message onthe monitor, a bell, or the like.

If the caregiver notices that the brain or cortical activity indicesdisplayed on the monitor are substantially different and/or indicativeof some neuropathological activity 39 such as seizure, stroke, or someother neurological problem, then the caregiver initially determineswhether the neuropathological activity is occurring contemporaneously,or at the present time 41. If the neuropathological activity isoccurring at that time, then the caregiver immediately notifies theappropriate clinician or administers the necessary treatment ormedication 43 to handle the activity and minimize damage to the subject.If the subject is not presently experiencing the indicatedneuropathological activity, but rather had suffered it in the past, thenthe clinician annotates the portion of the subject's EEG signal 45 fromthe hemisphere that shows the past activity for future reference and/ortreatment.

FIG. 3 is a flowchart showing the process of monitoring a subject'sstatus with regard to cortical or brain activity as a measure ofwakefulness or awareness or reaction to noxious or surgical stimulationusing the bilateral monitoring system and method. A subject is attachedto the bilateral monitoring system with an electrode array that measuressignals from both hemispheres of the subject's brain (not shown).Preferably, the electrode array involves the placement of electrodes onthe subject's head in such a manner that the measurement electrodes aresubstantially equidistant from the center of the subject's head whichcorresponds to the longitudinal fissure of the brain separating the twobrain hemispheres along the sagittal plane of the subject's body. Alsopreferably, at least two measurement electrodes are placed substantiallysymmetrically as described, at least one measurement electrode beingplaced on each side of the subject's head to measure the brain orcortical activity of each brain hemisphere. A reference electrode isplaced in the center of the subject's head, substantially near thelocation of the longitudinal fissure (not shown). Once the electrodearray is in place, the subject's brain or cortical activity in eachbrain hemisphere is monitored at substantially the same time 47.

After monitoring the subject's brain or cortical activity for eachhemisphere, the subject is anesthetized or sedated 49, and when thesubject is fully anesthetized or sedated, the brain or cortical activityin each of the subject's brain hemispheres is then measured individuallybut at substantially the same time 51 and preferably on a continuousbasis. The measurements are performed on each hemisphere via themeasurement electrode on for the given hemisphere and the commonreference electrode along the longitudinal fissure (not shown). As theEEG signal is monitored and measured from each brain hemisphere, thesystem calculates individual brain or cortical activity indices 53 foreach of the subject's brain hemispheres that quantifies the subject'sbrain or cortical activity, corresponds to the level of wakefulness orawareness, or conversely the level of sedation, that each of thesubject's brain hemispheres are experiencing. These brain or corticalactivity indices range between the values of zero (indicating braindeath) and 100 (indicating complete wakefulness and awareness)—howeverother types of indices may be used as well. As these indices arecalculated for each brain hemisphere, they are displayed substantiallyin real time and substantially at the same time on a monitor 54 for thecaregiver to see and use to evaluate the needs of the subject.Optionally, the method can include a warning or message (not shown) tothe caregiver indicating a significant difference between the twoindices. This warning or message can be a flashing light, a message onthe monitor, a bell, or the like.

If the indices displayed are substantially different for each of thesubject's brain hemispheres or they indices begin to change, or in someother way indicate that there is a change in the subject's brain orcortical state or brain activity, the caregiver notices this change inthe displayed indices 55. When this occurs, the caregiver must determinewhere in the treatment process the subject is 57. If the subject is donewith the given treatment, process or procedure for which it was sedatedor anesthetized, then the caregiver can either allow the subject tonaturally come out of the sedated or anesthetized state or canadminister medication 59 to return subject to alert state more quickly.If the indices show that the subject is becoming alert, or that onebrain hemisphere is more alert than the other (though the total effectis that the subject appears fully sedated or anesthetized) and it is notthe appropriate time for the subject to come out of sedation oranesthesia, then the caregiver can adjust the level of medication oradminister additional medication as necessary to increase the level ofsedation and return the hemisphere(s) back to a state of no alertness,wakefulness or awareness.

FIG. 4 is a flow chart showing a process of closed-loop delivery ofmedication utilizing a least-risk approach to minimize the level ofmedication needed to sedate or anesthetize a subject while maintaining asufficient level of sedation or anesthesia ensuring the patient is notalert or awake during the procedure, treatment or process. A subject isattached to the bilateral monitoring system with an electrode array thatmeasures signals from both hemispheres of the subject's brain (notshown). Preferably, the electrode array involves the placement ofelectrodes on the subject's head in such a manner that the measurementelectrodes are substantially equidistant from the center of thesubject's head which corresponds to the longitudinal fissure of thebrain separating the two brain hemispheres along the sagittal plane ofthe subject's body. Also preferably, at least two measurement electrodesare placed substantially symmetrically as described, at least onemeasurement electrode being placed on each side of the subject's head tomeasure the brain or cortical activity of each brain hemisphere. Areference electrode is placed in the center of the subject's head,substantially near the location of the longitudinal fissure (not shown).Once the electrode array is in place, the subject's brain or corticalactivity in each brain hemisphere is monitored at substantially the sametime 63.

After monitoring the subject's brain or cortical activity for eachhemisphere, the subject is anesthetized or sedated 65, and when thesubject is fully anesthetized or sedated, the brain or cortical activityin each of the subject's brain hemispheres is then measured individuallybut at substantially the same time 67 and preferably on a continuousbasis. The measurements are performed on each hemisphere via themeasurement electrode on for the given hemisphere and the commonreference electrode along the longitudinal fissure (not shown). As theEEG signal is monitored and measured from each brain hemisphere, thesystem calculates individual brain or cortical activity indices 69 foreach of the subject's brain hemispheres that quantifies the subject'sbrain or cortical activity, corresponds to the level of wakefulness orawareness, or conversely the level of sedation, that each of thesubject's brain hemispheres are experiencing. These brain or corticalactivity indices range between the values of zero (indicating braindeath) and 100 (indicating complete wakefulness and awareness)—howeverother types of indices may be used as well. As these indices arecalculated for each brain hemisphere, they are displayed substantiallyin real time and substantially at the same time on a monitor 71 for thecaregiver to see and use to evaluate the needs of the subject.Optionally, the method can include a warning or message (not shown) tothe caregiver indicating a significant difference between the twoindices. This warning or message can be a flashing light, a message onthe monitor, a bell, or the like.

Rather than a caregiver continuously monitoring the brain or corticalactivity indices for changes in subject status, brain or corticalactivity, or neuropathological activity, predetermined thresholds areused for closed-loop medication delivery to indicate to the system whenthe subject shows signs of such changes or conditions in the subject.The system initially uses the brain or cortical activity indicescalculated for each of the subject's brain hemispheres to determinewhether either one or both of the hemispheres shows signs of wakefulnessor alertness 73 which indicates the subject's brain is coming out ofsedation or anesthesia in the corresponding hemisphere. As long asneither QEEG index shows signs of wakefulness or awareness in either ofthe subject's brain hemispheres, the system continues to monitor andmeasure the individual hemispheres' EEG signals and calculate thecorresponding indices 74. However, if at least one of the brain orcortical activity indices indicates that the corresponding brainhemisphere is becoming alert or waking, then the system next attempts todetermine the level of anesthesia or sedation medication that hasalready been administered to determine whether the subject is close tooverdose of said medication 75.

The determination of overdose, or near overdose, of medication is madeas a function of the difference between brain or cortical activityindices in each of the subject's brain hemispheres. If the QEEG index ofone hemisphere indicates that it is becoming alert, and the QEEG indexof the other shows similar signs, then it is likely safe for ananesthetist or appropriate caregiver to administer additional sedativeor anesthesia medication 77 to return the subject to sufficient levelsof sedation or anesthesia. However, if the QEEG index relating to brainor cortical activity of one brain hemisphere shows signs of becomingalert and the other shows signs of continued deep sedation oranesthesia, then it is not safe to administer additional medication orthe subject would run the risk of overdosing. In such event, thecaregivers must cease treatment and tend to the subject as necessary 79in order to prevent harm to the subject either through lack of sedationor overdose thereof.

FIG. 5. is a flow chart depicting a process of delivering a message to acaregiver utilizing the bilateral monitoring system and method by whichthe caregiver is notified of any type of significant change oroccurrence in the subject's status, brain or cortical activity, orcondition. A subject is attached to the bilateral monitoring system withan electrode array that measures signals from both hemispheres of thesubject's brain (not shown). Preferably, the electrode array involvesthe placement of electrodes on the subject's head in such a manner thatthe measurement electrodes are substantially equidistant from the centerof the subject's head which corresponds to the longitudinal fissure ofthe brain separating the two brain hemispheres along the sagittal planeof the subject's body. Also preferably, at least two measurementelectrodes are placed substantially symmetrically as described, at leastone measurement electrode being placed on each side of the subject'shead to measure the brain or cortical activity of each brain hemisphere.A reference electrode is placed in the center of the subject's head,substantially near the location of the longitudinal fissure (not shown).Once the electrode array is in place, the subject's brain or corticalactivity in each brain hemisphere is monitored at substantially the sametime 81.

After monitoring the subject's brain or cortical activity for eachhemisphere, the subject is anesthetized or sedated 83, and when thesubject is fully anesthetized or sedated, the brain or cortical activityin each of the subject's brain hemispheres is then measured individuallybut at substantially the same time 8 and preferably on a continuousbasis. The measurements are performed on each hemisphere via themeasurement electrode on for the given hemisphere and the commonreference electrode along the longitudinal fissure not shown). As theEEG signal is monitored and measured from each brain hemisphere, thesystem calculates individual brain or cortical activity indices 87 foreach of the subject's brain hemispheres that quantifies the subject'sbrain or cortical activity, corresponds to the level of wakefulness orawareness, or conversely the level of sedation, that each of thesubject's brain hemispheres are experiencing. These brain or corticalactivity indices range between the values of zero (indicating braindeath) and 100 (indicating complete wakefulness and awareness)—howeverother types of indices may be used as well. As these indices arecalculated for each brain hemisphere, they are displayed substantiallyin real time and substantially at the same time on a monitor 89 for thecaregiver to see and use to evaluate the needs of the subject.Optionally, the method can include a warning or message (not shown) tothe caregiver indicating a significant difference between the twoindices. This warning or message can be a flashing light, a message onthe monitor, a bell, or the like.

As the brain or cortical activity QEEG index of one or both of thesubject's brain hemispheres rises corresponding to a change in thesubject's status, condition, or the occurrence of some neuropathologicalactivity, the system monitors the rise. If at least one of the QEEGindices reaches a predetermined threshold value, the system determinesthat the corresponding hemisphere is experiencing a change 91, such asbecoming alert or wakeful or experiencing neuropathological activity.When the system makes this determination it then delivers a message to acaregiver 93 who can address the change in the subject accordingly. Thismessage can be delivered in numerous ways: visual display on themonitor, audible notification such as a beep indicating attention isnecessary, or through telecommunications networks such as sending a pageor text message to the appropriate caregiver's pager or phone. Uponreceiving the message from the system that a change has occurred and thesubject needs some form of attention, the caregiver can go to thesubject and administer the appropriate care or attention 95.

FIG. 6 is a schematic of one embodiment of a display of two indicescalculated corresponding to the brain or cortical activity of asubject's brain hemispheres. The display 96 in this embodiment is usedto show the right 97 and left 99 brain hemispheres' brain or corticalactivity or level of consciousness. The brain or cortical activity QEEGindex is calculated by one or more of the steps listed above. The QEEGindex for the right brain hemisphere, in this example, is surrounded bycolored box 98 (shown as shading), the color which is coordinated withan orange electrode lead (not shown) attached to the right ride of thesubject's head (not shown). Similarly, the brain or cortical activityQEEG index is calculated and displayed for the left brain hemisphere 99.The QEEG index for the left brain hemisphere, in this example, issurrounded by a yellow box 100 (shown as a different level of shading)which is coordinated with a yellow electrode lead (not shown) attachedto the left ride of the subject's head (not shown). Additionalinformation such as the suppression ratio (left hemisphere) 101 andsuppression ratio (right hemisphere) 103 for each brain hemisphere,which represents the amount of time with no substantial brain orcortical activity, may also be incorporated into the display 96.Optionally, the QEEG indices can display just the index numbers 97 and98 where the actual number, rather than the surrounding box is colorcoded.

FIG. 7 is a schematic of another embodiment of a display showing the twocalculated indices and additional information related to the subjectbeing monitored. In this display 104, the individual brain or corticalactivity indices 106 & 107 for each brain hemisphere are shown in theupper right portion 105 of the display 104 displayed in color (notshown) corresponding, as described above, preferably to the electrodelead used (not shown).

The individual raw EEG waveforms 109 & 110 for each brain hemisphere aredisplayed in the upper left portion 108 of the display 104. Thewaveforms preferably are displayed in color (not shown) matching thecolor of the corresponding QEEG index 106 & 107 as well as thecorresponding electrode (not shown) lead acquiring the given signal. Inthis embodiment, the right brain hemisphere EEG waveform 109 and QEEGindex 106 are displayed in orange while the left hemisphere EEG waveform110 and QEEG index 107 are displayed in yellow. If a spike is recordedin one of the hemisphere EEG waveforms displayed indicating that somebrain or cortical activity has occurred, the corresponding brain orcortical activity QEEG index would also rise indicating a higher levelof consciousness, wakefulness or awareness than expected.

The schematic also shows in the left center portion 111 of the screen,what is referred to as the trend screen 112 which graphically maps thechanges in each hemisphere's calculated QEEG index over time 115. Again,the trend line for each brain hemisphere's brain or cortical activityQEEG index is displayed in color (not shown) corresponding to thedisplayed QEEG index number, EEG waveform, and electrode lead. Thisgraph serves to map the changes in the brain or cortical activityindices and helps the caregiver to correlate increases in brain orcortical activity with the corresponding EEG waveform. Similar to above,rises in EEG activity shown in the raw waveform would be reflected inthe QEEG index relating to brain or cortical activity. However, if itwas a momentary or short-lived increase in brain or cortical activity,which may indicate the onset of subject arousal for example, thecaregiver might not see it in the real-time QEEG index display. Thisindex map allows the caregiver to see the history of the QEEG indexvalues.

Also displayed in the lower left portion 113 of this schematic is agraphical representation of the measured EMG component 114 of the EEGsignal from each brain hemisphere. Again, the EMG signal is displayed incolor (not shown) corresponding to the QEEG index display color for thebrain hemisphere for which the EMG is recorded. The EMG portion of thesignal is recorded and filtered out of the EEG signal so it does notcorrupt or intrude on the EEG signal. It is also recorded so that thecaregiver can correlate any muscle activity, as reflected in the EMGsignal, with increases in the EEG waveform and therefore with the brainor cortical activity indices. It provides a more complete picture of theoccurrences leading to any changes in the brain or cortical activityindices that may be registered.

Additionally, electrode information is displayed simultaneously with theabove monitoring components in the right center portion 116 of theschematic. The symbol for each electrode is labeled (electrode 1 117,reference 118, ground 119, and electrode 2 120 in this example) and eachsymbol is displayed in color (not shown) corresponding to the hemisphereof the subject's brain it is recording an EEG signal from. The impedance(electrode 1 121, reference 122, ground 123, and electrode 2 124 in thisexample) measured for each electrode is also shown in this portion 116of the display. Also shown are two level bars: one 125 indicating theamount of noise being picked up in the EEG signals, and one 126representing the percentage of the signal that is artifact corrupted.Together, these components give the caregiver a reference as to howaccurate and clear the EEG signal is that is being recorded. The systemuses all of the measured and calculated electrode information to make adetermination of the electrode or sensor connection and resultant signalquality and displays this determination 127 on the screen.

FIG. 8 is a schematic of another embodiment of the present inventionshowing the brain or cortical activity indices for each of the subject'sbrain hemispheres along with the corresponding EEG waveforms in amagnified view. In this display 128, the individual brain or corticalactivity indices 130 & 131 for each brain hemisphere are shown in theupper right portion 129 of the display 128 and are preferably displayedin color (not shown) corresponding, as described above, preferably tothe electrode lead used (not shown).

On the left portion 132 of the display 128 in this embodiment, the twoindividual EEG waveforms 133 & 134 are displayed with no other waveformor additional information. The waveform 133 for the right brainhemisphere is displayed on top and in color (not shown) corresponding,as described above, preferably to the electrode lead used (not shown).The waveform 134 for the left brain hemisphere is displayed on top andin color (not shown) corresponding, as described above, preferably tothe electrode lead used (not shown).

The lower right portion of the display 128 presents a selection menu 135which gives the caregiver options for different views or embodiments toemploy. The caregiver can select to display a trend page (not shown) byselecting the Trend Page button 136. The caregiver can select to displayan EEG waveform page 132 by selecting the EEG Page button 137. Thecaregiver can select to display a spectral page (not shown) by selectingthe Spectral Page button 138. The caregiver can select to display astatus page (not shown) by selecting the Status Page button 139. Byselecting one of these buttons, the display 128 would be altered toinclude the selected page.

FIG. 9 is a schematic of another embodiment of the present inventionshowing an electrode impedance signal quality check process using thebilateral monitoring system and method. In this display 140, althoughthe upper right portion 141 of the display is still shown for theindividual brain or cortical activity indices 142 & 143 for each brainhemisphere, the individual brain or cortical activity indices 142 & 143are not calculated or displayed because there is no EEG signal beingtransmitted and measured during electrode impedance and signal qualitycheck.

The left portion 144 of the display 140 shows a large representativeimage of a subject's face 145 with images 146-149 corresponding to theplacement of the electrodes used (electrode 1 146, reference electrode147, grounding electrode 148, electrode 2 149). Also shown on the leftportion 144 of the display 140 are the labels 150-153 with measuredimpedance values corresponding to each electrode 146-149 on thesubject's head 145. In this particular embodiment, the referenceelectrode 147 has been measured and shown to have high impedance, whichis displayed on the screen 151. The measurements of the other electrodes146, 148, 149 are normal and actual measurements are not given 150, 152,153.

Alternatively, the right center portion 154 of the screen presentsanother view of electrode signal quality. This signal quality display154 also gives individual representations 155-158 of the electrodes(electrode 1 155, reference electrode 156, grounding electrode 157,electrode 2 158). Additionally, since the measured impedance of thereference electrode 156 was calculated (not shown) to be too high, avisual indicator message 159 is displayed on the screen pointing outthat the impedance of that electrode is high. Similar indicators wouldbe shown for any of the other electrodes if necessary. Also shown aretwo level bars: one 160 indicating the amount of noise being picked upin the EEG signals, and one 161 representing the percentage of thesignal that is artifact corrupted. Together, these components give thecaregiver a reference as to how accurate and clear the EEG signal isthat is being recorded. The system uses all of the measured andcalculated electrode information to make a determination of theelectrode or sensor connection and resultant signal quality, andinstructs 162 the caregiver when attention is required.

FIG. 10 is a schematic of another embodiment of a display showing thetwo calculated indices and additional information related to the subjectbeing monitored. In this display 163, the individual brain or corticalactivity indices 165 & 166 for each brain hemisphere are shown in theupper right portion 164 of the display 163 displayed in color (notshown) corresponding, as described above, preferably to the electrodelead used (not shown).

The individual raw EEG waveforms 168 & 169 for each brain hemisphere aredisplayed in the upper left portion 167 of the display 163. Thewaveforms preferably are displayed in color (not shown) matching thecolor of the corresponding QEEG index 165 & 166 as well as thecorresponding electrode (not shown) lead acquiring the given signal. Inthis embodiment, the right brain hemisphere EEG waveform, 168 and QEEGindex 165 are displayed in orange while the left hemisphere EEG waveform169 and QEEG index 166 are displayed in yellow. If a spike is recordedin one of the hemisphere EEG waveforms displayed indicating that somebrain or cortical activity has occurred, the corresponding brain orcortical activity QEEG index would also rise indicating a higher levelof consciousness, wakefulness or awareness than expected.

A general status page is shown in the lower left portion 170 of thedisplay 163 with various indicator views 170, 175, 180, 183 andmeasurements displayed simultaneously. This optional view portrays tothe caregiver multiple information sources regarding various aspects ofthe EEG signal acquisition process, all at the same time, rather thanchoosing one or two display at a given time. Each of these subscreensgives a textual overview of some portion of the EEG signal ormeasurement process that can be shown in greater detail or in graphicalform in some other optional display described in several of the otherfigures.

One such indicator view is the signal quality portion 171 of the statuspage 170. This portion displays measurements for both EEG electrodes171, 172 being collected, each electrode corresponding to one of thesubject's brain hemispheres. Various measurements regarding signalquality can be displayed here including, but not limited to, thepresence of artifacts in each electrode and the spectral power of eachelectrode at various frequencies.

Another indicator view is the electrode contact portion 173 of thestatus page 170. This measurement is closely related to signal quality,but focuses on the fidelity of the connection between the electrodes orother sensors and the subject's body. The system performs thismeasurement as a function of the electrical impedance of each electrodeor sensor. The system then displays the measured impedance value foreach of the electrodes or sensors used: grounding electrode 174, firstmeasurement electrode 175, reference electrode 176, and secondmeasurement electrode 177.

Yet another indicator view is the spectral powers measurement portion178 of the status page 170. This portion displays measurements for bothEEG electrodes 179, 180 being collected, each electrode corresponding toone of the subject's brain hemispheres. Various measurements of thespectral powers of the EEG signal from each hemisphere of the subject'sbrain can be displayed here. The powers of each spectral band or waveletof the original parent EEG waveform are displayed.

Still another indicator view is the data acquisition portion 181 of thestatus page 170. This portion displays measurements regarding thequality of the data being recorded by the system from the EEG signalfrom each hemisphere of the subject's brain. The system can determinethe level of data integrity 182 and display that in the data acquisitionwindow, as well as the detection of electrostatic units that may bedetected and potentially interfere with the data acquisition anddecrease the quality integrity of the recorded data.

The lower right portion of the display 163 presents a selection menu 184which gives the caregiver options for different views or embodiments toemploy. The caregiver can select to display a trend page (not shown) byselecting the Trend Page button 185. The caregiver can select to displayan EEG waveform page 132 by selecting the EEG Page button 186. Thecaregiver can select to display a spectral page (not shown) by selectingthe Spectral Page button 187. The caregiver can select to display astatus page (not shown) by selecting the Status Page button 189. Byselecting one of these buttons, the display 163 would be altered toinclude the selected page.

FIG. 11 is an image of another embodiment of a display showing the twocalculated indices and additional information related to the subjectbeing monitored. In this display 190, the individual brain or corticalactivity indices 192 & 193 for each brain hemisphere are shown in theupper right portion. 191 of the display 190 displayed in color (notshown) corresponding, as described above, preferably to the electrodelead used (not shown).

The individual raw EEG waveforms 195 & 196 for each brain hemisphere aredisplayed in the upper left portion 194 of the display 190. Thewaveforms preferably are displayed in color (not shown) matching thecolor of the corresponding QEEG index 192 & 193 as well as thecorresponding electrode (not shown) lead acquiring the given signal. Inthis embodiment, the right brain hemisphere EEG waveform 195 and QEEGindex 192 are displayed in orange while the left hemisphere EEG waveform196 and QEEG index 193 are displayed in yellow. If a spike is recordedlit one of the hemisphere EEG waveforms displayed indicating that somebrain or cortical activity has occurred, the corresponding brain orcortical activity QEEG index would also rise indicating a higher levelof consciousness, wakefulness or awareness than expected.

The lower left portion 197 of the display 190 presents a spectral powersview of the EEG signals from each of the subject's brain hemispheres.The spectral graphs 198 & 199 corresponding to the EEGs signal from eachbrain hemisphere are shown in this area when selected by the caregiverin the selection menu 200.

The lower right portion of the display 190 presents a selection menu 200which gives the caregiver options for different views or embodiments toemploy. The caregiver can select to display a trend page (not shown) byselecting the Trend Page button 201. The caregiver can select to displayan EEG waveform page 194 by selecting the EEG Page button 202. Thecaregiver can select to display a spectral page 197 by selecting theSpectral Page button 203. The caregiver can select to display a statuspage (not shown) by selecting the Status Page button 204. By selectingone of these buttons, the display 190 would be altered to include theselected page.

FIG. 12 is an image of another embodiment of a display showing variousBEG waveforms collected from a subject and several spider chartsgraphically representing data collected from those EEG signals. Thedisplay 205 window is divided into separate areas, each providingdifferent information to the user. In the embodiment portrayed in thisfigure, the left portion 207 of the display 205 is displaying multipleEEG waveforms 209 being collected from the subject. Each EEG waveform209 represents a separate channel that is connected to the subject.These channels correspond to EEG electrodes (not shown) placed on thesubject's head (not shown) which transmit the displayed EEG waveforms209 to the monitoring equipment and thus to the display 205.

The upper right portion 211 of the display 205 in this particularembodiment displays three spider graphs 213, 215, 217 for the user tosee and evaluate. The topmost spider chart 213 depicts the calculatedQEEG index for each incoming EEG channel as its calculated value out ofa maximum possible value of 100. Also in the upper right portion 211 ofthe display 205, the lower left spider chart 215 portrays theelectromyography (EMG) component measured in each channel of the EEGsignal, and the lower right spider chart 217 presents the suppressionratio of each EEG signal corresponding to the length of time duringwhich no substantial EEG signal or brain activity was recorded.

The lower right portion 219 of the display 205 in this particularembodiment portrays two further spider charts. In this portion of thescreen, the left spider chart 221 portrays the electrical impedancemeasured in each of the EEG electrodes attached to the subject. Theright spider chart 223 in this embodiment presents the power of the 60Hz interference (or 50 Hz in, for instance, Europe) measured in each EEGchannel attached to the subject and corresponding to the environmentalnoise.

These spider charts are another display option available to the user todisplay on the monitor along with options discussed in other embodimentsabove, all in all providing the user with a robust menu of choices andcombinations for displaying many types and varieties of data eitherindividually or in conjunction with each other in numerous embodimentsof the present invention.

1-20. (canceled)
 21. A method of detecting a change in subject statuswith a device for quantifying brain or cortical activity in the subjectas a function of depth of sedation or anesthesia comprising the stepsof: a. anesthetizing or sedating a subject; b. monitoring the subjectwith a brain having a left hemisphere and a right hemisphere, thesubject under anesthesia or sedation and being monitored with a devicefor quantifying brain or cortical activity as a function of depth ofsedation or anesthesia, the device with at least two measurementelectrodes, and at least one reference electrode, the at least twomeasurement electrodes comprising at least one electroencephalogram(EEG) electrode, having a signal, positioned to monitor left hemispherebrain or cortical activity and at least one EEG electrode, having asignal, positioned to monitor right hemisphere brain or corticalactivity of the subject's brain, the reference electrode comprising atleast one EEG electrode, each electrode providing an EEG analog signalwhich is subsequently converted to a digital signal; c. measuring thebrain or cortical activity of both the subject's left and right brainhemispheres essentially simultaneously over a period of time part of theperiod of time over which the subject is under sedation or anesthesia;d. calculating based in part on the digital signals with the processorat least one numerical quantitative electroencephalogram (QEEG)time-series index corresponding to the brain or cortical activity as afunction of depth of anesthesia or sedation of each of the left andright hemispheres of the subject's brain over the period of time part ofwhich the subject is under sedation or anesthesia; e. displaying the atleast two numerical time-series indices, with at least one numericaltime-series index corresponding to the brain or cortical activity ofeach of the left and the right hemispheres over the period of time partof the period of time which the subject is under sedation or anesthesiaon a monitor simultaneously; f. comparing the numerical time-seriesindices of each hemisphere's cortical activity as a function of depth ofanesthesia or sedation; and g. determining based on the calculatedindices for each hemisphere whether differences between the brain orcortical activity of one hemisphere of the brain is indicative of achange in subject status when compared to the brain or cortical activityof the other hemisphere of the brain of the subject.
 22. The method ofclaim 21 wherein the change in subject status corresponds to a reactionof the subject following noxious stimulation.
 23. The method of claim 21farther comprising an additional step, the additional step is comparingthe calculated numerical brain or cortical activity indices for each ofthe subject's brain hemispheres and determining, based at least in parton the differences between the at least two numerical QEEG time-seriesindices, whether the signal of one or more of the EEG electrodes haspoor signal quality.
 24. The method of claim 21 further comprising anadditional step, the additional step is comparing the calculatednumerical brain or cortical activity time-series indices for each of thesubject's brain hemispheres and determining whether the subject hassuffered, or is suffering some neuropathological activity based ondifferences between the indices.
 25. The method of claim 21 wherein theindices are calculated using a wavelet transform or a Fast Fouriertransform.
 26. The method of claim 21 further comprising an additionalstep, the additional step is treating the subject by administrating adrug or therapeutics to said subject based on a comparison by aprocessor, clinician or physician of at the least two quantitativeelectroencephalographic time-series indices corresponding to the brainactivity as a function of depth of anesthesia or sedation of the brainregion of the subject.
 27. A method for comparativeelectroencephalography in monitoring brain function as a function ofanesthesia or sedation in a plurality of distinct brain regions of thesame subject on a continuous and substantially concurrent basis,comprising the steps of: a. applying at least oneelectroencephalographic measurement electrode at each of said pluralityof brain regions, and applying at least one reference electrode, andcoupling each measurement and reference electrode to a control andprocessing system; b. continuously acquiring an analogelectroencephalographic signal from each of said electroencephalographicmeasurement electrodes; c. converting the analog electroencephalographicsignal from each of said electroencephalographic measurement electrodesto a digital signal; d. separately and concurrently calculating for eachsaid digital electroencephalographic signal at least one numericalquantitative electroencephalographic time-series index representative ofthe brain activity as a function of depth of anesthesia or sedation ofthe brain region corresponding to the measurement electrode; e.concurrently visually displaying on a monitor at least one numericalquantitative electroencephalographic time-series index for each of atleast two distinct brain regions; and f. administrating a drug ortherapeutics to said subject based on a comparison by a processor,clinician or physician of the at least two quantitativeelectroencephalographic time-series indices corresponding to the brainactivity as a function of depth of anesthesia or sedation of the brainregion.
 28. The method of claim 27 further comprising an additionalstep, the additional step is comparing the at least two quantitativeelectroencephalographic time-series indices corresponding to the brainactivity as a function of depth of anesthesia or sedation of each brainregion and determining, based at least in part on the differencesbetween the at least two quantitative electroencephalographictime-series indices, whether the signal of one or more of the EEGelectrodes has poor signal quality.
 29. The method of claim 27 furthercomprising an additional step, the additional step is comparing the atleast two quantitative electroencephalographic time-series indicescorresponding to the brain activity as a function of depth of anesthesiaor sedation of each brain region and determining, based at least in parton the differences between the at least two quantitativeelectroencephalographic time-series indices, whether the subject hassuffered, or is suffering some neuropathological activity based ondifferences between the indices.
 30. The method of claim 27 wherein theindices are calculated using a wavelet transform, a spectral process ora Fast Fourier transform.
 31. A method for quantifying brain or corticalactivity in the subject as a function of depth of anesthesia comprisingthe steps of: a. anesthetizing a subject; b. monitoring the subjecthaving a brain with a left hemisphere and a right hemisphere, thesubject under anesthesia, and the monitoring with a device having atleast two measurement electrodes, and at least one reference electrode,the at least two measurement electrodes comprising at least oneelectroencephalogram (EEG) electrode, having a signal, positioned tomonitor left hemisphere brain or cortical activity and at least one EEGelectrode, having a signal, positioned to monitor right hemisphere brainor cortical activity of the subject's brain, the reference electrodecomprising at least one EEG electrode, each electrode providing ananalog EEG signal which is subsequently converted to a digital signal;c. measuring the brain or cortical activity of both the subject's leftand right brain hemispheres essentially simultaneously over a period oftime part of the period of time over which the subject is underanesthesia; d. calculating based in part on the digital signals with theprocessor at least one numerical quantitative electroencephalogram(QEEG) time-series index using a wavelet transform or a Fast Fouriertransform, and corresponding to the brain or cortical activity as afunction of depth of anesthesia of each of the left and righthemispheres of the subject's brain, over the period of time part ofperiod of time which the subject is under anesthesia; and e. displayingsimultaneously at least one numerical time-series index corresponding tothe brain or cortical activity of each of the left and right hemispheresover the period of time on a monitor.
 32. The method of claim 31,further including an additional step of treating the subject byadministrating a drug or therapeutics to said subject based on acomparison by a processor, clinician or physician of at the least twoquantitative electroencephalographic time-series indices correspondingto the brain activity as a function of depth of anesthesia or sedationof the brain region of the subject.
 33. The method of claim 32, whereinthe treating of the subject is done by the administration of the drugusing the processor, which is a closed loop processor.
 34. The method ofclaim 33, wherein the closed loop processor utilizes a least riskapproach based on the calculated QEEG indices corresponding to each andboth the right and left hemispheres of the subject's brain.
 35. Themethod of claim 31, further comprising an additional step, theadditional step comparing the calculated numerical brain or corticalactivity indices for each of the subject's brain hemispheres anddetermining, based at least in part on the differences between the atleast two numerical QEEG time-series indices, whether the signal of oneor more of the EEG electrodes has poor signal quality.
 36. The method ofclaim 31, further comprising an additional step, the additional stepcomparing the calculated numerical brain or cortical activitytime-series indices for each of the subject's brain hemispheres anddetermining whether the subject has suffered, or is suffering someneuropathological activity based on differences between the indices. 37.The method of claim 31, wherein the indices are calculated using awavelet transform or a Fast Fourier transform.
 38. The method of claim37, wherein a bispectral index is calculated utilizing a Fast Fouriertransform.
 39. The method of claim 31, further including notifying acaregiver to identify when the subject requires attention or there is apotential problem with the device.
 40. The method of claim 39, whereinthe caregiver is notified by a message, a signal or a combination.